I do not object to people looking at their watches when I'm speaking. But I strongly object when they start shaking th

1. I do not object to people looking at their watches when I'm speaking.But I strongly object when they start shaking them to make sure they are still going. William Norman Birkett

2. FDA Regulation of Laboratory Developed Tests AMDM Annual Meeting April 23, 2009 Bradley Merrill Thompson

3. Topics • A Tale of Two Petitions • Legal basis for FDA regulation of LDTs • Competing policy proposals for LDTs • Where are the Feds going? • In policy making? • In enforcement? • How should this be resolved? I feel like Zsa Zsa Gabor’s fifth husband. I know what I'm supposed to do but I don't know if I can make it interesting. Al Gore

4. A Tale of Two Petitions

5. A Tale of Two Petitions

6. A Tale of Two Petitions

7. Topics • A Tale of Two Petitions • Legal basis for FDA regulation of LDTs • Competing policy proposals for LDTs • Where are the Feds going? • In policy making? • In enforcement? • How should this be resolved? Politics gives guys so much power that they tend to behave badly around women. And I hope I never get into that. Bill Clinton

8. Laws aren’t always clear Robertstevensonfiles.com

9. FDA Jurisdiction Medical Device Connection To Commerce FDA Jurisdiction + = FDA Jurisdiction Held for Sale Interstate Commerce Device Intended Use = + + +

10. Device Definition • The statutory definition of “device” is: • [An instrument, apparatus, implement, machine contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory. • The FDCA further qualifies the definition, providing that a product constitutes a “medical device” if it, among three alternatives, is “intended for use in the diagnosis of disease or other conditions … in man or other animals”. • FDA regulation defines invitro diagnostic products (IVDs) as: • “[Those reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae.”

11. Device Definition

12. Device Definition

13. Prohibited Acts FDCA Section301(k) on “prohibited acts” applies to devices: • “Held for sale (whether or not the first sale) • After shipment in interstate commerce” Plus other sections of 301 can apply. My mother never saw the irony in calling me a son-of-a-bitch.Jack Nicholson

14. Prohibited Acts

15. Prohibited Acts

16. The Law is There to Protect Us Innocentenglish.com

17. Bottom Line: FDA Jurisdiction • FDA believes it has statutory authority to regulate LDTs, if it chooses. • In the 1997 Preamble to the Final Rule for Analyte Specific Reagents, FDA made clear: • FDA believes that clinical laboratories that develop [in‑house] tests are acting as manufacturers of medical devices and are subject to FDA jurisdiction under the act. • IVDMIA and ASR guidance

18. Topics • A Tale of Two Petitions • Legal basis for FDA regulation of LDTs • Competing policy proposals for LDTs • Where are the Feds going? • In policy making? • In enforcement? • How should this be resolved? Winter related injuries occur more often in the winter.-newswoman for WHIZ-TV, Zanesville, Ohio

19. Competing Policy Proposals At least 5 • AdvaMed • California Healthcare Institute (CHI) • American Clinical Laboratory Association (ACLA) • Coalition for 21st Century Medicine • Secretary's Advisory Committee on Genetics, Health, and Society

20. Scope ACLA FDA Cleared/Approved Tests IVDMIA AdvaMed CHI SACGHS Molecular diagnostics LDTs 21st Century

21. Fundamental Elements

22. FDA Oversight

23. Other Major Facets Attorney: Now doctor, isn’t it true that when a person dies in his sleep, he doesn’t know about it until the next morning?-testimony from court records

24. Topics • A Tale of Two Petitions • Legal basis for FDA regulation of LDTs • Competing policy proposals for LDTs • Where are the Feds going? • In policy making? • In enforcement? • How should this be resolved?

25. New Developments • Dr. Gutman retirement; Don St. Pierre acting director • Possible new permanent director before OIVD move in June • OIVD received additional funding and personnel • Net +25 FTEs • Now has regulatory counsel

26. Policy Level • LDT legal and policy status • Per OIVD, they will not be the decision-makers on what happens • Goal is that policy changes will be transparent and not a surprise Attorney: You say the stairs went down to the basement?Witness: Yes.Attorney: And these stairs, did they go up also?-testimony from court records

27. Policy Level • ASR • Aftermath of Sept. 2007 guidance • Some premarket submissions • Some withdrawn from market • Some pre-IDE meetings and planning • OIVD has a risk-based inspection plan and field guidance

28. Policy Level • IVDMIA • Some history • Draft guidance issued – Sept 2006 • Written comments + Public meeting (Feb 2007) • Draft guidance reissued – July 2007 • Important issues involved • Scope and definition of IVDMIA • Labs coming into compliance with FDA requirements, e.g., overlapping CLIA and FDA regulation • Impact on innovation, patient access • Final guidance still in OIVD’s work plan

29. Policy Level • RUO/IUO • Not a pathway for keeping an ASR on the market • FDA may be watching this area closely Democracy used to be a good thing, but now it has gotten into the wrong hands.-Senator Jesse Helms

30. Topics • A Tale of Two Petitions • Legal basis for FDA regulation of LDTs • Competing policy proposals for LDTs • Where are the Feds going? • In policy making? • In enforcement? • How should this be resolved?

31. Development of FDA’s “Not Invented There” Doctrine

32. 2004 WL to Correlogic Systems • Addressed software for the OvaCheck test, sold to LabCorp and Quest • Correlogic operated a reference lab. • FDA permitted all three labs to continue to offer the test service, but objected to the sharing of the software. • Said the software was a device, and it was sold to two labs, so it did not qualify as an LDT

33. 2007 WL to EXACT Sciences Corp • PreGen-Plus assay was “designed, developed, validated, and marketed by Exact” • “Exact provided instructions for use, validation information, and performance claims to LabCorp.” • Equipment and reagents required for the test are specified by Exact, and in some cases supplied by Exact. • Therefore, the test is a medical device and requires clearance. • There is another side to this story, but the point is FDA’s enforcement arguments of choice.

34. 2008 WL to LabCorp The perfect storm: • High risk test • Patient and professional complaints • Might be an IVDMIA • Unproductive meeting with FDA (no compromises) • Yale product

35. 2008 WL to LabCorp • Relied on information obtained from LabCorp, including a press release and a technical bulletin, as well as information provided by LabCorp in a meeting with FDA • “test []was designed, developed, and validated by investigators at Yale University and not LabCorp” • “[IFU] and performance characteristics appear to have been developed by Yale investigators.” • “This device is not within the scope of laboratory developed tests over which the agency has traditionally exercised enforcement discretion”

36. FDA’s Interim, Evolving Approach FDA will bring enforcement against labs and maybe others if there is evidence that the test was: Not Invented There I have always wanted to be somebody. I guess I should have been more specific.-Lily Tomlin

37. Recent $302M Quest Diagnostics Settlement • Whistleblower false claims suit • FDCA violations formed basis of suit – product in question was FDA-regulated and distributed by a Quest subsidiary • Labeling claims rendered product misbranded • Quest subsidiary distributed marketing materials describing their fully-automated assay as closely correlating with manual assays   • However, the company allegedly was aware their automated assay did not produce such correlated results • Complaint alleged false claims for the tests and unnecessary treatment that resulted because of the faulty test

38. Topics • A Tale of Two Petitions • Legal basis for FDA regulation of LDTs • Competing policy proposals for LDTs • Where are the Feds going? • In policy making? • In enforcement? • How should this be resolved? Lawyer: "You don't know what it was, and you didn't know what it looked like, but can you describe it?"

39. FDA should regulate all diagnostics The reasons for not regulating don’t hold water

40. Sometimes the Obvious Escapes Us I109photobucket.com

41. Red Herring 1—FDA Does Not Have the Resources to Regulate LDTs • The resources question doesn’t have anything to do with differentiatingbetween IVD kits and LDTs. • At most it means FDA can’t regulate all tests, so it should focus on the riskiest. • No evidence that LDTs are lower risk (don’t have equivalent data sets). • With user fees available, over the long haul it is no longer true.

42. Red Herring 2—FDA Regulation Will Discourage Innovation • Innovation can come from nearly any sector. • The LDT policy is not directed at giving more freedom or latitude specifically to those involved in innovation. • The LDT policy is both over‑inclusive and under‑inclusive when it comes to innovation. • The policy is under‑inclusive because there is plenty of innovation being done within manufacturing companies that needs to be encouraged, • The policy is over‑inclusive because many of the LDTs being developed are not at all innovative.

43. Red Herring 3—CLIA Regulation is Enough FDCA and CLIA are not the same. Unlike FDCA: • CLIA contains no mechanism for external review or approval of LDTs • CLIA lacks the quality systems requirements of the FDA regulations. • CLIA focuses only on standards of performance and laboratory processes, not on the quality of diagnostic tests made and used by the laboratories • CLIA contains no mechanism for post‑market vigilance and reporting parallel to that of the FDA regulations. • CLIA contains no mechanism for recalls of problematic LDTs. • CLIA does not contain the required reporting of corrections and removals that FDA regulations contain.

44. Red Herring 3—CLIA Regulation is Enough Either: • FDA regulation adds enough value to warrant applying it to LDTs, OR • FDA regulation does not add enough value to warrant applying it to LDTs, OR • The feds don’t know whether FDA regulation adds enough value or not. Which is it?

45. The Government’s LDT Policy is Hurting Patients Either: • LDTs are not safe enough because they lack the benefits of FDA regulation, OR • IVDs are delayed too long because they must comply with unnecessary FDA regulation. One of those must be true!

46. The Government Doesn’t Always Get it Right www.txrollergirls.com

47. FDA Knows How to Solve This

48. FDA Knows How to Solve This

49. FDA Knows How to Solve This

50. FDA Knows How to Solve This